Checkpoint inhibitors in ovarian cancer: A review of preclinical data

• Main Authors: David W. Doo, Lyse A. Norian, Rebecca C. Arend
• Format: Article
• Language: English
• Published: Elsevier 2019-08-01
• Series: Gynecologic Oncology Reports
• Online Access: http://www.sciencedirect.com/science/article/pii/S235257891930058X

Ovarian cancer is the deadliest gynecologic malignancy, and relapse after initial treatment is frequently fatal. Although ovarian cancer typically has an immunosuppressive tumor microenvironment, a strong intratumoral T cell presence is associated with an improved response to chemotherapy and better overall prognosis. Given the success of checkpoint inhibitors in the treatment of other malignancies, there has been an attempt to replicate these results in ovarian cancer clinical trials. Preclincal studies in ovarian cancer have also been conducted over the past decade, and most of the focus has been on the use of programmed cell death protein 1 (PD-1). Several other checkpoint inhibitors have also been investigated in various combinations with chemotherapy, oncolytic vaccines, co-stimulatory molecules, poly ADP ribose polymerase (PARP) inhibitors, and other checkpoint inhibitors. Unfortunately, these successes have yet to translate to the clinical realm. Whether this is because the drug class is truly ineffective in ovarian cancer, or simply because the research is lacking is unclear. Either way, it is evident that preclinical data on the use of checkpoint inhibitors is woefully deficient in ovarian cancer and more research is urgently needed to inform the translation of immune checkpoint blockade into successful clinical use. In this review, we discuss the results from preclinical studies using checkpoint inhibitors to treat ovarian cancer, with a focus on strategies that show potential for clinical use. Keywords: Ovarian cancer, Preclinical, Immune checkpoint inhibitors, Mouse model, Immunotherapy